Small-molecule aggregation inhibitors reduce excess amyloid in a trisomy 16 mouse cortical cell line.
We have previously characterized a number of small molecule organic compounds that prevent the aggregation of the beta-amyloid peptide and its neurotoxicity in hippocampal neuronal cultures. We have now evaluated the effects of such compounds on amyloid precursor protein (APP) accumulation in the CTb immortalized cell line derived from the cerebral cortex of a trisomy 16 mouse, an animal model of Down's syndrome. Compared to a non-trisomic cortical cell line (CNh), CTb cells overexpress APP and exhibit slightly elevated resting intracellular Ca2+ levels ([Ca2+] inverted exclamation mark). Here, we show that the compounds 2,4-dinitrophenol, 3-nitrophenol and 4-anisidine decreased intracellular accumulation of APP in CTb cells. Those compounds were non-toxic to the cells, and slightly increased the basal [Ca2+] inverted exclamation mark. Results indicate that the compounds tested can be leads for the development of drugs to decrease intracellular vesicular accumulation of APP in trisomic cells.
Paula Lima
Andréa C
AC
Program of Cell Biophysics and Biochemistry, Instituto de Bioquímica Médica, Universidade Federal do Rio de Janeiro, Rio de Janeiro, Brazil.
Arriagada
Christian
C
Toro
Rodrigo
R
Cárdenas
Ana María
AM
Caviedes
Raúl
R
Ferreira
Sergio T
ST
Caviedes
Pablo
P
D019297:2,4-Dinitrophenol / Q000494:pharmacology*; D000544:Alzheimer Disease / Q000378:metabolism*; D016564:Amyloid beta-Protein Precursor / Q000037:antagonists & inhibitors* / Q000378:metabolism; D000814:Aniline Compounds / Q000494:pharmacology*; D000818:Animals; D002460:Cell Line; D002540:Cerebral Cortex / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D004195:Disease Models, Animal; D004314:Down Syndrome / Q000378:metabolism*; D051379:Mice; D009596:Nitrophenols / Q000494:pharmacology*
D016564:Amyloid beta-Protein Precursor; D000814:Aniline Compounds; D009596:Nitrophenols; C013813:4-anisidine; D019297:2,4-Dinitrophenol; C049017:3-nitrophenol